Cucurbituril is the name given to a cyclic oligomer formed by linking six (6) glycoluril units via methylene bridges. However, to differentiate the various cucurbiturils, this compound is referred to in this specification as “unsubstituted cucurbit[6]uril”. The substituted cucurbituril decamethylcucurbit[5]uril was first synthesised and identified in 1992 by Flinn et. al. (Angew. Chem. Int. Ed. Engl., 1992, 31, 1475). The remaining unsubstituted cucurbit[4 to 12]urils and some substituted cucurbit[4 to 12]urils, were synthesised by Day et. al. as described in the applicant's international patent application No. PCT/AU00/00412 (WO 00/68232), and in parent application Ser. No. 09/959,770, incorporated herein by reference.
Unsubstituted cucurbit[6]uril was first described in the literature in 1905 in a paper by R. Behrend, E. Meyer and F. Rusche, Leibigs Ann. Chem.; 339, 1, 1905. The macrocyclic structure of unsubstituted cucurbit[6]uril was first described in 1981 by W. A. Freeman et. al., “Cucurbituril”, J. Am. Chem. Soc., 103 (1981), 7367-7368. Unsubstituted cucurbit[6]uril has a chemical formula of C36H36N24O12 and is a macrocyclic compound having a central cavity.
The internal cavity of unsubstituted cucurbit[6]uril has a diameter of about 550 pm, a depth of 650 pm with portals at either end about 400 pm across. This rigid cavity has been shown to have high selectively in binding a variety of medium-small molecules and in this regard reference is made to Cintas, P., J. Inclusion Phenomena and Molecular Recognition in Chemistry; 17, 205, 1994.
The preparation of unsubstituted cucurbit[6]uril has generally followed the procedure first described in the article by R. Behrend et. al. published in 1905.
In German patent no. DE 19603377, published Aug. 7, 1997, a process for synthesising unsubstituted cucurbit[6]uril is described. This process includes dissolving acetylene diurea (glycoluril) in an aqueous solution of a strong mineral acid in the presence of excess formaldehyde, with warming. The water is evaporated from the mixture to completely eliminate the water from the mixture. The remaining polymer mixture is then heated to a temperature up to 145° C. to complete the reaction. The applicants for DE 19603377 have stated that a yield of up to 82.4% of the theoretical yield can be obtained.
In German patent no. DE 4001139, the use of unsubstituted cucurbit[6]uril to remove organic compounds with hydrophobic groups, dyes, decomposition products from dyes and/or heavy metals from aqueous solutions is described. The patent actually states that a cyclic oligomer which is obtained by condensation of urea, thiourea, derivates of urea and/or derivatives of the thiourea with dialdehydes and formaldehyde is used. Although the patent states that the degree of polymerisation, n, of the cyclic oligomer varies between about 3 and about 8, the examples of the patent showing cyclic oligomers having a degree of polymerisation, n, only of 6. Example 1 shows the preparation of unsubstituted cucurbit[6]uril by heating glycoluril under reflux with formaldehyde.
Experiments conducted by the present inventors in following the procedure of Example 1 of DE 4001139 have shown that cucurbituril having 6 glycoluril units joined together is formed. In the words of DE 4001139, n=6 for this product. No evidence was found of any cyclic oligomer having a degree of polymerisation, n, other than 6. Indeed, a paper by Buschmann et. al., Inorgica Chimica Acta, 1992, 193, 93 states that under the synthetic conditions as described in DE 400 1139, only cucurbituril having a degree of polymerisation, n, of 6 is formed.